CN105934390A - Flexible container, system and method of manufacturing same - Google Patents

Abstract

A flexible container, system and method of manufacture can include an in-line system that allows flexible containers of varying sizes to be manufactured in a single relatively high speed and efficient production line and in a single clean room through the use of transport and exchange equipment configured to adeptly handle flexible containers throughout the process.

Description

Flexible container and manufacture system and manufacture method

The application is according to United States Code No. the 119th article of (e) moneys of volume 35, it is desirable to September 2 in 2013 The priority of the U.S. Provisional Application No. 61/872,833 that day submits to, the disclosure of which is overall with it It is incorporated herein by.

Background technology

1. technical field

Presently disclosed subject matter relates to the flexible container of storage and administration fluid and solution Manufacture system and manufacture method, more particularly, to providing for sterilely being formed, fill, Seal and pack the fully integrated continuous system of flexible sterilization container and the system of method and side Method, wherein said flexible sterilization container is used for storing and being administered intravenous injection (IV) material, all Such as medical science or the liquid of medicine, powder, gas or solution.

2. correlation technique discussion

Various liquids generally from sterilization container intravenously administrable (via IV) to patient.These solution Arbitrary medicine liquid can be included, such as replace body fluid, or even comprise medicament (medicine) Solution.Include having for storage solutions for storing and be administered the ordinary packing of these solution The flexible container of chamber.Outlet port is connected to the chamber for being administered, and passes through standard IV configuration carries solution to patient.

The flexible container manufactured under traditional handicraft typically requires the manufacturing process of multi-step, wherein shape Becoming empty container, then the most online lower sterilizing, completes on the line of return thereafter to fill and finishing Technique.The method of this separation produces waste of material and low process efficiency, causes higher Cost and manufacturing time increase, and pollute or other destruction container or its content integralities Potential risk increase.

Summary of the invention

Embodiment of the present disclosure describes for sterilely shaping, fill, seal and packing The fully-integrated system and method for flexible container, this flexible container is for storing and being administered such as The IV material of medical solution.In one embodiment, container is by the single plane of polymer Sheet material is formed, and described sheet material may be the sheet material of lamination, wherein folds described sheet material to limit appearance Surface or front and back sides before and after device.Volume shell is by having high oxygen and moisture barrier character Material is constituted, and described material makes thermoplastic container long term storage not make the content of container drop Solve.Then volume shell can be made to expand, before forever stretching out with compressed gas or liquid Portion and/or rear portion sheet material, thus increase volume of a container capacity.In another embodiment, Container include the transparent front sheet material that by polymer and may make for the plane layer of laminated material and Relative rear sheet material.Rear sheet material is made up of the plane layer of that be similar to or identical polymeric material. Along common periphery, front sheet and rear sheet material are sealed, form volume shell.But, Another alternative embodiments of container comprises the multiple chambers separated by peelable seal, is used for Accommodate diluent and at least one medicament.Peelable seal is made to rupture by handling container, thus will Content, i.e. diluent and medicament mix, for flowing to suffer from by conventional IV external member Person.

Embodiment of the present disclosure also describes the system for manufacturing flexible pouch, including: structure For the single enclosed environment for sterile processing；It is configured to manufacture flexible pouch and be positioned at closed-loop Domestic flexible pouch manufactures board；It is configured to flexible pouch sterilizing and is positioned at single enclosed environment Interior electron beam sterilization board；And be configured to at least two different materials filling of flexible pouches Filling board, this filling board is positioned at single enclosed environment.

Accompanying drawing explanation

Now with reference to the device be given by way of example, system and method exemplary Embodiment, and with reference to accompanying drawing, it is more fully described theme disclosed in the present application.Wherein:

Fig. 1 is the front view of the flexible container that the principle according to the present invention is made；

Fig. 2 is the side view of the flexible container that the principle according to the present invention is made；

Fig. 3 is that the plane of the embodiment of the container manufacturing device continuous, online according to the present invention is shown It is intended to；And

Fig. 4 is the flow chart of the example manufacturing process of the container of the principle according to the present invention.

Detailed description of the invention

As it has been described above, present invention provide for storing and being administered the material of such as medical solution The manufacture system of flexible container and manufacture method.The definition of flexible container can include but not limited to, It is not configured to keep the flexible pouch of himself shape, conventional IV bag, medicament molten under normal gravity Liquid bag and the U.S. Patent number 5,944,709 typically specified, 6,198,106,6,165,161, 6,203,535、5,910,138、5,928,213、6,468,377、6,117,123、6,846,305、 6,764,567 and 6, any vessel described in 966,951, above-mentioned patent is overall by quoting with it It is expressly incorporated herein.And the container described in text of the statement is described as flexible container or flexible pouch, The scope of the container of the present invention also include accommodating fluid, solid, spawn, powder, Gaseous material and the container of liquid, no matter whether it is intended to be consumed by humans and animals etc. or use.

Segmentation that flexible container can be separated by least one peelable seal or be separated into multiple chamber Room, such as two or three are with upper chamber.As described in above-mentioned United States Patent (USP), peelable seal is Rupturable, thus promote the mixing of content between each chamber.Such as, peelable seal is made Rupture and the content of chamber can be made to mix safely, and be not exposed to environment or touched by people. One chamber can be bigger than other chambers, or each chamber can be identical or big with size or volume Approximate on body.Liquid diluent can be accommodated, simultaneously as the first chamber of bigger chamber Other chambers can accommodate active constituents of medicine (API) and/or medicament, and it can be dry powder or liquid Any one of body.Other chambers can be empty, and restriction or formation make medicine and delivery end The cushion space of mouth separation or region.

When making one-level peelable seal rupture, the content in API accommodating chamber and diluent chamber Solution mixing in room.After being thoroughly mixed generation, two grades of peelable seals can be made to rupture, And mixed solution is delivered to patient or other target recipient via delivery port.One-level is peelable The cracking threshold sealed can be less than or be less than the cracking threshold of two grades of peelable seals so that one-level Peelable seal ruptured before two grades of peelable seals, so that API accommodating chamber and diluent hold The content received in chamber is mixing through buffer chamber with before delivery port.Container Design is any molten before stoping or being at least sufficiently mixed substantially prevented from the entire contents at container Liquid or the dry powder conveying by delivery port, thus reduce and individually use diluent composite medicine condition The medication error of association.It addition, the manufacture method of the flexible pouch of the disclosure eliminates in flexible pouch Manufacture and fill during, need extra structure and time demand with keep aseptic condition list Only shifting process and the additional risk polluted.When complex drug mixing in pharmaceutical environment During thing, any have the disappearing of possible technique being exposed to environment (and may pollute) condition Remove is all desired.The manufacturing process of the flexible pouch of the present invention can be fully identical controlled Atmosphere is carried out, without controlling the environment of independent transfer vessel between the part of technique.

Flexible container can be by transparent flexible plastic film and the screen of selectable cladding API chamber Barrier layer is formed.Barrier layer can be aluminium foil layer or other opaque thin layer or material.Optional Barrier layer can provide opposing may negative effect API chamber in accommodate drug substances light, Oxygen and the barrier of humidity.

The technique of the disclosure provides the flexibility ratio of increase on container dimensional, including increasing API Chamber and the volume of diluent chamber, the most also reduce manufacturing time and cost.As with reference to seeing Point, it was noted that the flexible container described in above-mentioned patent can provide receiving 50mL dilution The diluent chamber of agent and the most 4.0g powder pharmaceuticals of receiving or the API chamber of API.

The manufacturing process of the flexible container of the disclosure allow for the container dimensional increased, bigger chamber Building volume (such as, such as can accommodate the diluent chamber of the diluent of such as more than 250mL), And bigger API weight/volume scope (such as more than 8.0g).It should be noted that it is logical The API chamber of the technique formation crossing the disclosure can accommodate the API of all kinds or form, all Such as liquid, gel, powder, capsule, particle etc..Can be formed relatively by the technique of the disclosure Big flexible container comprises the packing volume of diluent chamber and for the API of other type medicine Packing volume/the weight of chamber, this is impossible for the less container manufactured traditionally. The manufacturing process of the disclosure can the opening on top and bottom by being limited to bag, be located in continuously Manage the container as bag.Flexible container can be with fully-integrated aseptic manufacturing process, continuously Formation, sterilizing, filling and seal, this can reduce process waste and manufacturing cost, simultaneously It is easier to ensure that aseptic condition.

The embodiment of the flexible container of the disclosure consider to use can provide firm sealing and And the various materials of final products can be protected in the intended pot-life.Main film material Material includes various polymeric material, includes but not limited to PET 60/40 6mil, Excel 80,/20 8 Mil, PET/SiOx/80/20 6mil, PET/80/20 6mil and combinations thereof etc..Implement at some In mode, it is possible to add silica (SiOx) barrier in membrane structure.

In Traditional flexible carrier, aluminum foil screen barrier layer is arranged on conduct in rear side or back surface Diluent chamber and the optical barrier of API chamber, and be set on the front surface as may be only Optical barrier for API chamber.Enforcement at the flexible container manufactured by the technique of the disclosure In example, aluminium foil barrier can be arranged on the both sides of API chamber or two surfaces with to wherein holding The barrier for moisture, oxygen and light needed for the active component offer received.It addition, be positioned at soft Property the front side of container or front surface on aluminium barrier can be peelable, to provide for enabling With use before and/or the machine of the visible defects of the content of visual inspection API chamber during it Meeting.

The flexible container of the disclosure can include the end with 80/20PP/Kraton material compositions Mouthful.This composition prevents the damage that may be caused by excessive puncture force.This material also eliminates Mandrel is used to support the needs of port during fusion process.Holding for filling flexible of the disclosure The technique of device process is not suitable for using mandrel during seal process, because during seal process Port is made independently to keep its shape to be favourable.The use of 80/20PP/Kraton blend provides Harder manufactured goods, it allows port to keep its character under stress, facilitates again acceptable Puncture force.

Present invention additionally comprises the embodiment printing coating process after providing sterilizing, this technique bag Including the preprinted label of use, this label can comprise eight kinds of colors of the most each label.Mark Label can printing standard product information the most in advance.The most human-readable coding lot number and The various data of Expiration Date can use such as black TTR print head to be directly printed on and beat in advance On the label of print.Coded data can include that barcode format is tieed up in 1 peacekeeping 2.

Flexible container according to embodiment of the present disclosure manufacture also keep separate diluent chamber and The integrality of the one-level peelable seal of API chamber, until when using.In order to ensure peelable Being sealed in and keep complete in transport and normal processing procedure, flexible container can along one-level Shell sealed folded and fasten.In order to keep the folded structure of flexible container, it is possible to pressure-sensitive by two grades Continuous pressing device for stereo-pattern is applied to flexible container.Continuous pressing device for stereo-pattern guarantees that flexible container is in folded structure, and And still allow for end user and launch container in use.

The flexible container system of the disclosure allows to produce various container dimensionals, includes but not limited to dilute The packing volume releasing agent is such as 50mL, 100mL, 250mL and more than 500mL Container.

The flexible container of the disclosure can include firsts and seconds peelable seal, described peelable seal Can before enabling the diluent chamber of partitioned bottle, API chamber and transmit buffer chamber.? In one embodiment, the width of peelable seal can be about 4.0mm to about more than 10.0mm. In another embodiment, the width of peelable seal is about 7.0mm.

The flexible container of the disclosure is to protect the side of flexible container in intended traffic condition whole process Formula constructs, and is used for transporting.Various corrugated box structures can be used in accommodating flexible container, including But it is not limited to be intended to every case and preserves the 250mL corrugated tank of 24 containers.At an embodiment In, corrugated body adds wax layer.This wax layer minimizes during intended traffic condition mainly The abrasion of container and corrugated body dirt.Optionally can add center H type in body structure Separator.

Fig. 1 and 2 illustrates exemplary flexible container, and it can be by example described herein Sexual system and method manufacture.With reference to Fig. 1 and 2, it is shown that manufactured according to the present invention is exemplary Container 10.Although container 10 can be checked with any orientation, but for purposes of illustration, join Describing the chamber of container position each other according to the orientation of Fig. 1 and Fig. 2, Fig. 1 illustrates soft Property container front view, and Fig. 2 illustrate the flexible container along Fig. 1 line 2-2 intercept side cut Face figure.Container 10 can be by the front sheet 12 of roughly planar and relative roughly planar Rear or tergite material 14 (only figure 2 illustrates) is formed.Front sheet 12 and tergite material 14 can It is made up of the flexible material of individual layer or the multilayer laminate of flexible material.

The sheet material 12 and 14 forming container 10 can provide respectively, and along common plane 15 relative to each other dispose (Fig. 2).Will with sealed-for-life then along common periphery 16 Sheet material 12 and 14 is sealed.Seal common periphery 16 along container 10 whole outside Zhou Yanshen, thus form the first chamber 17.Structure and width that periphery seals can change.Energy Enough opening 18 is set on the top surface of container 10, this opening 18 enables container to load, Hang or be otherwise affixed to such as support on support.Alternately, front sheet 12 and the back of the body Sheet material 14 can be by folding single thin-film sheet and with any existing or exploitation in the future close Envelope technique will be peripherally sealed together and be formed.

In the illustrative embodiments of Fig. 1 and 2, container 10 is separated into three separate chamber: First or upper chamber 17, second or middle part chamber 19 and the 3rd or lower chamber 20, depend on Intended application in container 10, it is possible to each chamber sterilizing.Upper chamber 17 and center lumen Room 19 is separate by the first peelable seal 25, simultaneously in the middle part of chamber 19 and lower chamber 20 Separate by the second peelable seal 26.In other embodiments of the present invention, it is possible to only Between upper chamber 17 and middle part chamber 19, peelable seal is set.In these embodiments, Sealing between middle part chamber 19 and lower chamber 20 can be by being applied hydraulic coupling by user And rupture, promote the content of upper chamber 17 and middle part chamber 19 to enter lower chamber 20.

It is sufficiently solid to allow the normal place of container that term used herein " peelable " seals Reason does not make sealing rupture and does not make the content of chamber by mistake mix, but again specific behaviour Crackly sealing under Zong, it makes sealing area under the hydraulic coupling by handling container applying Interior front sheet and rear sheet separation, thus allow mixing and the distribution of container contents.Peelable Sealing can be by by polymeric material portion present on the adjacent inner surface of front sheet and rear sheet material Divide and fuse together and formed.Such as, sealing is obtained by heat-sealing process, in heat seal work In skill, time, temperature and pressure along with change apply heat and pressure to regional area, these To describe in greater detail below.Peelable seal is made to rupture the content peace that can allow for chamber Full mixing, and be not exposed to environment or touched by people.It should be understood that a chamber can With bigger than other chambers, or each chamber can be size or volume identical or generally similar.

In an application of container 10, upper chamber 17 liquid dilution agent is filled, and Middle part chamber 19 medicament is filled, and all is become by the pharmaceutically active of user or people digest as expected Point or other nutrition or auxiliary element, it can be to include liquid, gel, gas or solid shape Any form of formula provides.Lower chamber 20 can act as the secure interface of outlet port 30, And until container prepares to use remains sky.In this embodiment, upper chamber 17 Can accommodate liquid diluent, simultaneously in the middle part of chamber 19 can accommodate medicine, active constituents of medicine (API), nutritional labeling or other auxiliary elements, can be the most arbitrarily dry powder, gel, solid Any one in body or liquid.

To contact now Fig. 3, describe manufacturing step and the device of the container 10 of Fig. 1 and 2.This Disclosed device and step are suitable for manufacturing front sheet and tergite material has single or multiple lift The container of laminate film.Also, it is understood that can be according to the module placement of the component of Fig. 3 And change quantity, shape, structure and the position that container seals.

Fig. 3 is the half of the illustrative embodiments of the most online machine for manufacturing containers or system 300 Schematic plan view, it is shown that various sealings form board, main thin-film network (primary film web) Feed rolls, electron beam emitter platform, API load arrangement and the position of board etc..Fig. 3 illustrates bag Wound membrane (bag roll film) module 302, it provides for container front sheet and the batch of tergite material Material.Bag volume module 302 is arranged on the input of machine for manufacturing containers 300, makes main film Bag can be loaded into the bag formation section of production line.Film is loaded into operation can be according to production-line technique Remainder is carried out the most automatically.The cutting mechanism that can be provided for continuous operation (does not shows Go out), and sufficient film accumulation can be provided thus allow appropriate volume replacing construction.Energy Enough use for suitably interweaving and being loaded into the visual guide of main film, explanation or machine intuitively Device designs.All mechanical assistance that volume operation and process need should not interfere with the properly functioning of equipment. Can control and monitor tension force and the track of main film roll.Whole appropriate polices can be set Report, includes but not limited to that net is damaged or loses tension force.

Film integrator 304 receives film from bag film module 302 and feeds into clearer 306, This clearer 306 is at film forming cleaning film before being formed as container.For instance, it is possible to Main film is loaded at board and keeps net cleaner and the contact of ionized gas supply, thus protects Hold clean environment, make the particle accumulation on main film roll minimum.Net cleaner can be automatic It is monitored, and the warning operation when needs periodically intervene (e.g., change and adhere to paper using) Person.

Manufacturing machine 300 and can farther include module 309, the most peelable paper tinsel is loaded into production line Bag formation section.Module 309 includes paper tinsel volume 310 and integrator 312, and this integrator 312 is by paper tinsel Feeding into rotation die cutter 318, this rotation die cutter 318 is set to cut into paper tinsel Required form.In this stage, peelable paper tinsel is cut/is cut into that it is ultimately constructed, and transport with It is welded on main film.Paper tinsel is loaded into operation can be appropriate according to the remainder of production-line technique Ground is carried out automatically.Splicing body can be set, be used for operating continuously.Sufficient paper tinsel can be provided Accumulate thus allow appropriate volume replacing construction.Can use for suitably interweaving and being loaded into master Want the visual guide of film roll, explanation or machine design intuitively.Module 309 can also include For warning the assembly of operator when peelable paper tinsel cigarette closely exhausts, and the intervention of operator is That need and can carry out.All mechanical assistance needed for volume operation and process are not disturbed and are set Standby is properly functioning.Can control and monitor tension force and the track of peelable paper tinsel volume.Can arrange complete The appropriate alarm in portion, includes but not limited to that net is damaged or loses tension force.Can monitor continuously can The cutting of stripping paper tinsel and separation, to monitor inappropriate alignment or inappropriate final cutting.Can Use vision and audible alarm, thus any mistake or defect are taked school by warning operator at once Just take action.Arbitrary trimming operation can be designed, to minimize the generation of predetermined substance (PM), And prevent any PM from moving on product.Module 309 can also include that automating waste material removes System 320.

Machine for manufacturing containers 300 can also include film folder 308, this film folder 308 Main film is folded to form bag, obtains flexible container from this bag.Alternative is use two Roll up main film and be incorporated into together, being easier to keeping parallelism arrangement also such that it is able to provide The method avoiding blocking.Main film can be folded along the center line of main net.Should be always Correctly keep film orientation.In one embodiment, when being merged together, opposed The arrangement of peelable chaff is maintained at about ± 1.5mm within.Excessive film can be monitored " walk about ". Vision and audible alarm can be set, warn operator when needs are intervened.Can monitor any Net damaged, block or lose tension force.Appropriate alarm can be set, alert when needs are intervened Show operator.

Cutting board and paper tinsel Heat sealing machine 314 can also be set.In this stage, it is possible to by cutting Peelable paper tinsel seals to main thin-film network.Peelable paper tinsel can correctly align and be positioned main film On.Vision and audible alarm can be used, thus any arrangement needing operator to intervene is asked Topic warning is to operator.The position of peelable paper tinsel fusion instrument can be adjusted, and change as required Become to adapt to product configurations.All relevant technological parameters, such as temperature, pressure and resident time Between, it is possible to automatic either manually or by such as CPU, PLC or other controller at this board Ground monitoring continuously controls with independent.Vision and audible alarm can be used, thus exceed any Technological parameter outside regulation warns to operator.This system can be configured to compensate stopping of machine Stop and start situation, to avoid the excessively fusion to Primary containers of the peelable paper tinsel or fusion not enough.

Machine 300 can also include one-level peelable seal board 316.At this board, machine 300 Can be configured between diluent chamber and medicament/API chamber automatically apply one-level peelable close Envelope.Main film can be directed at rightly at peelable seal board and position.Peelable seal instrument Minimum peelable seal width, such as 7mm can be provided.Can monitor and individually control all Relevant technological parameter, such as temperature, pressure and residence time.Vision and the sense of hearing can be used Alarm, thus warn any to operator beyond the technological parameter outside regulation.Can basis Needs arrange cooling board and monitor.

Machine 300 can also include that peripheral sealing (side) fuses board 330.At this board On 330, machine 300 automatically applies side periphery and seals each container.Main film can be can Stripping seals board 316 and is directed at rightly and positions.All relevant technological parameters, such as temperature, Pressure and residence time can monitored and individually control.Vision and audible alarm can be used, Thus warn any to operator beyond the technological parameter outside regulation.Can set as required Put cooling board 332 and monitor.If employing cooling board, then can to its design with Avoid condensation.

Machine also includes cutting machine 322, this cutting machine 322 can include punch board, Corner cut board and trimming board.The edge of cutting machine 322 automatic cutting container, and be used for Open the folded sides of container.These boards can also determine the overall length of each flexible container. For each various sizes of container, it is possible to suitably mark and the position of location cutting sword.As Fruit uses heated blade, then can monitor the most relevant technological parameter.Can suitably extract by Any potential waste gas that this technique causes.The whole useless of generation can be automatically removed at board 324 Material.

Now, the container of formation enters bag transfer board 340, is transferred to electron beam sterilization unit. It is defeated that each (partly building) flexible container is transferred to electron beam bag by bag transfer board 340 Send machine 342.This mechanism can be suitable for various various sizes of container.Can eliminate before transfer All bags not properly formed at board before.Bag transporter 342 can be properly oriented to And open, to receive container formed as discussed above.Flexible container can in transport establishment just Really position, and forward can be kept in whole transfer process to orient.Bag transporter 342 Can close as suitably desired and breech lock.

The bag transporter 342 that can also be referred to as carrier is set by electron beam at the container formed or bag Container or bag is fixed during standby processing.In one embodiment, transporter 342 is with 36m/min Speed or be equal to 60 bag operating rates per minute the container of formation be carried through electronics Bundle processes.Transporter 342 be also configured to can to rotate during electron beam treatment 180 ° (if Need, can be more than 360 °), thus multiple sides of the bag of formation are exposed to sterilizing spoke Penetrate, minimize the over-exposure for main film simultaneously.Can be carried out this on the major axis of bag Rotate.Alternately, shuttle mechanism 341 can be configured to during electron beam treatment rotate bag (if it is required, 180 ° or more than 360 °).In one embodiment, transporter 342 structure Cause so that vessel level (flatly) is loaded to carry out electron beam treatment.Real at another Executing in mode, transporter 342 is configured to vertically load bag to carry out electron beam treatment.Transport Each embodiment of machine is configured in the range of whole action move, and the scope of action includes But be not limited to around x, y and z axes arbitrary or whole 0 to 360 degree rotation, axle include but not It is limited to the major axis of bag.

Electron beam sterilization chamber and technique be will be described in further detail now.In final filling and shaping Before being used for loading the isolation network of medicament/API, electron beam chamber is for being formed before and/or in entrance Flexible container provide sterilizing.The most relevant technological parameter can be monitored.Vision can be used And audible alarm, thus warn any to operator beyond the technological parameter outside regulation.Bag Transporter 342 can be configured to during processing revolve turnback, to be equally exposed flexible appearance The both sides of device.Can suitably monitor and run this upset technique with automatic anti-fault pattern.Energy Enough eliminate any container performing the most definitely and rotating.Can monitor and warn and electron beam Run the exception in consistent all sparks, electric arc, voltage/current spike or other technique.As Fruit is abnormal to be occurred, then affected all containers in can suitably eliminating this cycle.Should set Put all safety that the electron beam irradiation to technique, X-ray accessory substance and ozonation by-product are relevant Precautionary measures and machine guard.Shielding should be enough to prevent any escaping radiation.Contemplated , exhaust system uses ozone purifier.System provides between normal production period, The ability of random bag sample was collected before electron beam board.Can be set up this in systems special Levy.Can in radiometer quality research a few days ago, online lower provide that collects to have radiation The bag of gauge.As required, bag can be to manufacture in nearest production run, and from Three different batches.System can be configured with and be loaded into equipped with putting before electron beam board Penetrate the ability of the bag of gauge, by electron beam treatment, and collect the bag of radiation.Can be in system In set up this as quality inspection pattern or manual mode.Can not be carried out this between normal production period ?.But, this step is the fastest and the easiest, then go back to produce the rapidest.Can be after the cleaning But sample before decontamination.System can have the dose delivery with 2kGy to 60kGy Carry out the ability that checking runs.Dose delivery can be accurate to ± 10% or 1kGy, takes it higher Person.System can be constructed to ensure that for lead without exposing.In other words, it is possible at constructing system Stainless steel in comprise lead screen.System can be configured with monitoring line speed, electronics Beam power consumption, pulsation rate and the ability of spark discharge.System can also be included in indoor ozone Level is more than the automatic anti-fault pattern in 0.3ppm or other emergency situations.

Machine is also provided with container shift module 344, is shifted from electron beam conveyer by container To filling board and/or isolation part 370.Single container is turned by this module 344 from electron beam chamber Move, import and fill board and/or isolation part 370.Mechanism 344 can be suitable for various different size Container.Conveyer can be suitably orientated and open, to remove container from electron beam chamber. Container suitably can orient at graded region before entering filling board and/or isolation part 370 And location.Container can be suitably orientated, and is fixed on main conveyer.Transfer work Skill can be configured such that does not damages fill system and/or the aseptic of main isolation network.At figure In the embodiment of 3, container moves in filling board and/or isolation part 370 in a counterclockwise direction Dynamic.

The manufacture system of the disclosure can include several for opening bag with filling medicament/API chamber Mechanism.In one embodiment, as it is shown on figure 3, shedding mechanism 346 is in chamber The sucker using driving before conveying powder or liquid separates main film.For opening bag or appearance Other embodiments of device include: use fixture to separate relative laminate film, use gravity to divide It is thin that vibrational energy that is that point to from relative laminate film, use or that focus on separates relative lamination Film, use the relative laminate film of magnetic separation, to use orientation liquid to separate relative lamination thin Film etc..

Mechanism also includes the isolator 348 for filling container with medicament/API.Thus, once Laminate film has already turned on or is separated from each other, chamber by be opened and expose and prepare fill out Fill.Then can move injection nozzle or injection nozzle is pointed to opening end, and being allowed to logical Cross opening in chamber, inject medicament/API.The shape of opening is big so that minimize spilling of liquid And promote the fast transfer of liquid, thus improve the speed of integrated artistic.Nitrogen cleans also can Enough before the filling of and then medicament/API etc., it is readily incorporated in technique.Due on top The opening that relatively large reception (and removing) nitrogen in chamber cleans, cleaning process also is able to Than in Traditional flexible bag, known process is faster.

Medicament/API be will be described in further detail now and fill the embodiment of board/isolation part 370. This module is responsible for mealy medicine/API is filled the medicament/API chamber to container.It addition, can The structure of two grades of peelable seals is carried out at this board.Powder can be filled board and be designed to minimum Change or eliminate conversion (changeover) parts.Can monitor and control each filling hopper continuously In powder level.Powder level in any one hopper is less than keeping abundant filling process During required minimum level, it is possible to use the sense of hearing and visual alarm warning operator to intervene. The hopper not conforming to rule can be identified definitely by system controller.Via using appropriate safety The HMI controlled can individually control and change and is delivered to each flexible container by fill system Powder filling weight target.Powder filling mechanism should be able to be in following exemplary scope and precision In target, distribution target powder filling weight exactly:

Can have periodic test and fill the ability of the medicament/API weight to container.Powder Medicament/API filling mechanism can receive periodic feedback from inspection weight process, and according to needing Adjust.The most crucial dosage process can be monitored the most continuously.These parameters can be wrapped Include servo loading, spiral rotating, scraping blade rotation etc..Powder medicine/API dosage mechanism can carry For minimizing the mechanism of potential product dirt.The filling line of powder medicine/API can be Under the region that two grades of peelable seals will position.Can use shielding body or applying nozzle with Prevent powder building up on two grades of peelable seal lines.The structure energy of two grades of peelable seals Enough after powder dosage, carry out at once at same board.Before applying two grades of peelable seals, The movement of container should be minimized.Peelable seal instrument can provide the minimum peelable seal of 7mm Width.All relevant technological parameters, such as temperature, pressure and residence time can be monitored And individually control.Can use vision and audible alarm, thus by any beyond regulation outside Technological parameter warns to operator.

Embodiment of the present disclosure is except solid or powder, it is also contemplated that liquid preparation/API.Existing Exemplary liquid fill system module and technique will be described in further detail.This module is used for will Liquid is filled to the chamber of container.It addition, two grades of peelable seals can be carried out at this board. Liquid filling machine platform can be designed, to minimize or to eliminate converting member.Can be by applying nozzle It is designed to minimize water clock.Any water clock the most should not pollute sealing surfaces.Liquid reservoir can be incorporated to Or pressure regulation pond, to avoid padding to lack liquid.Can by appropriate mechanism, such as quality or Volume, monitors available liquid continuously.When needs are intervened, the sense of hearing and visual alarm can By low for liquid level warning to operator, to avoid padding to lack liquid.Can be by using just When the system of security control individually control and change to be delivered to each container by fill system Liquid volume.The liquid volume being delivered to each container can be provided continuously by liquid filling machine structure Feedback.If using mass flow sensor to be used for feeding back, it may be considered that the liquid of dosage Character.Can set up in systems and to keep standard recipe and to verify the accuracy of continuous feedback Ability.Liquid filling machine structure can distribute target in following scope and precision target exactly Liquid volume:

Liquid-mixing measuring mechanism can provide the mechanism minimizing liquid splash and foaming.Filling out of liquid Filling line can be under the region that two grades of peelable seals will position.Can use shielding body or Applying nozzle is to prevent liquid building up on two grades of peelable seal lines.Two grades peelable close The structure of envelope should be after liquid dosage, carry out at same board at once.Can applying two grades Before stripping seals, it should minimize the movement of container.Peelable seal instrument can provide 7mm's Minimum peelable seal width.Can monitor and all relevant technological parameters of independent control, such as Temperature, pressure and residence time.Vision and audible alarm should be used, thus exceed any Technological parameter outside regulation warns to operator.

It follows that seal container at peelable seal board 350.Machine 300 also includes that port is inserted Enter and fuse board 360, being used for container outlet port is installed.Exemplary port be will now be described Insert and fusion board.This module is for oriented containers port in a reservoir, and permanent seal Transfer chamber.Single port can be suitably orientated and position.Can wrap with nondirectional batch Dress, supplies port or port to isolation network.Port inserts board and sealing mechanism can energy Enough minimize particulate matter (PM) to produce, and provide for getting rid of owing to normal port processes behaviour Make the mechanism of any PM produced.One can be inserted exactly in the transfer chamber of each container Individual (1) port.The final position of port can meet all applicable product figure and the rule of offer Lattice.Port can permanent seal in container, and complete any final fusion operation.Final molten Conjunction can not have any functional defect, such as crack, wrinkle, bubble, folding line or hole. It can be avoided that visual defects, the most too much cut or abrasion.Can monitor and independent control institute There are relevant technological parameter, such as temperature, pressure and residence time.Vision can be used and listen Feel alarm, thus warn any to operator beyond the technological parameter outside regulation.

Thereafter being provided with bag flip module 370, this bag of flip module 370 overturns bag to prepare liquid Body is filled.Module 370 is responsible for oriented containers, fills for diluent.Container can be orientated The opening of diluent chamber fills board towards diluent.Automatic anti-fault mechanism can be used to fit Locality orients and is directed at each container definitely.Rotation/flip module 370 can be configured to not Any part of container is caused damage.Firsts and seconds can be protected in rotary course peelable Seal not by excessive strength.Can protect port not by any scraping, abrasion or vestige. Should not damage the integrality of removable paper tinsel barrier.Can be by this procedure construction for avoiding in processing Period introduces any particulate matter in diluent chamber.Can shield rightly.

Then at liquid filling machine platform 356, with the Liquid-filled containers of such as diluent.Contact Medicament above/API fills described in isolation part 348, and liquid filling machine platform 356 can wrap Include the nozzle filling container with diluent.Exemplary diluent be will be described in further detail now fill out Charging system and process.This module is for filling diluent to the diluent chamber of container.Liquid Body is filled board and can be designed to minimize or eliminate converting member.Board can include following spy Levying: applying nozzle, it is designed as minimizing water clock, and it is close that any water clock is not the most polluted Envelope surface；And the liquid diluent pond that is incorporated to or pressure regulation pond, to avoid padding to lack liquid. Can be by appropriate method, such as quality or volume sensor, monitor available liquid continuously Body diluent.When needs are intervened, low for liquid level warning can be given by the sense of hearing and visual alarm Operator, to avoid padding to lack liquid.Can be by using the system of appropriate security control Individually control and change the liquid diluent volume being delivered to each container.Liquid diluent is filled Mechanism can provide provides continuous print feedback to the liquid volume being delivered to each container.If made It is used for feeding back with mass flow sensor, it may be considered that the character of the liquid of conveying.Can be System is set up and keeps standard recipe and verify the ability of accuracy of continuous feedback.Liquid is filled Mechanism can be in following scope and precision target, distribution target liq volume exactly:

Liquid diluent dosage mechanism can be configured to minimize splashing and the foaming of liquid.Permissible Use shielding body or applying nozzle as required.

Then, after the diluent chamber of flexible container deposited in by diluent, container moves Move to sealing board 358, apply to seal the final sealing of the top opening of container.A reality Execute in mode, seal board 358 and be set to complete container perimeter sealing at diluent chamber.? In this step, before applying final sealing, it should minimize the movement of container.A reality Execute in mode, when allowing process time, it is possible to carry out at the board identical with diluent filling Finally seal to avoid product to move and to splash.Can be at this moment by container permanent seal.Seal The final fusion of the periphery of diluent chamber should not have any functional defect, such as crack, Wrinkle, bubble, folding line or hole, and not there is visual defects, the most too much cut or Abrasion.The final technique that bag seals also includes monitoring and controls various technological parameters, such as temperature Degree, pressure and residence time.In one embodiment, technique also includes vision and/or the sense of hearing Alarm, for warning any to operator beyond the technological parameter outside regulation.In this stage Any final cutting carried out or suspension bracket punch operation, it is possible to minimize shot-like particle (PM) product Raw mode is carried out.Then bag transfer board 360 is moved the containers into, with along preparation container Carry out conveyer belt 362 transfer vessel packed.

The embodiment being used for manufacturing flexible container of the disclosure includes removing from main conveyer Container is also oriented to exit isolation network by single container.In this process step, it is possible to will hold Device orients and removes from main conveyer, and containment system is not produced not excessive stress. Carefully avoid Primary containers or the excessive wear of port, cut or vestige.Can appropriately keep The orientation of container is to exit isolation part.

Flexible container can move back in the way of entering aseptic isolation network to avoid any potential pollutant Go out isolation part.By applying at any duck eye opening and normal pressure can be kept to promote this effect Really.Can monitor and independent control all relevant technological parameters, such as temperature, pressure and stay Stay the time.Vision can be used and listen Feel alarm, thus warn any to operator beyond the technological parameter outside regulation.

The embodiment manufacturing flexible container of the disclosure can also include for setting in supplier Execute the technique carrying out FAT, can accept with checking finishing line and meet expectation Specification.FAT can include inspection and the equipment school of the equipment design of file record Accurate determination.The information obtained from these check can be used in establishment and contains equipment setting, adjusts Written procedure whole, that calibrate, safeguard, be monitored and controlled.

FAT also comprises the steps: to make an inventory and arranges in the bill of materials that supplier submits to The stock of the primary clustering gone out；Determine the installations and facilities of needs, its size, pressure, flow velocity etc., And its position connected；Check the material verification table that system component provides；Check primary clustering Specification, to ensure compliance with this specification；Check the label of assembly；Check checking collection volume；Inspection Look into the key equipment suitably run or the adjustment of needs guaranteeing equipment；And predetermined amount of time " manoeuvre " that do not use assembly is tested.

One of target of FAT is to judge whether machine can run true rightly Under the conditions of meet the requirement of qualification test (IQ/OQ/PQ).

Main processing isolation part and the embodiment of technique will be described.This module is closed the most aseptic Technique, and play the main barrier effect that the microorganism for final products pollutes.Isolation part is wrapped Enclose and disclosure satisfy that whole ISO 5 isolation part requirements, and can include following: Merlon door； 340 stainless steels (SS) structure；Enter door-forward sealing/vacuum control or compression seal；Gloves Hole；Aseptic can remove/replace gloves；Positive pressure gradient；Requirement for cleaning；Central drainage system； Air-treatment/ventilation；And the volume/dead band of minimum.

It is described below the compatible explanation of VHP.System can have following features: built-in Decontamination unit；Back-up capability-movable units can be connected when built in unit fault；6 times right Number reduces by 4 times of logarithms of comparison and reduces；And inflation ppm target.

The embodiment of main conveyer be will be described in further detail now.This module provides use In the main method that container is carried through whole sterile production technique.This mechanism can include by The ability that container vertical rotary is 180 °, thus by vessel port towards appropriate padding.Fortune Send mechanism can be suitably orientated and open, for receiving the container from electron beam chamber.Fortune The normal consume sending mechanism can be designed as adapting to elapse in time and to occur.Carrying out calmly In the case of phase safeguards, normal consume should not affect overall accuracy and the performance of system.Transport Mechanism can process all applicable container dimensionals.Can suitably minimize or eliminate converter section Part and the change of instrument.In whole aseptic processing, it is possible to be directed at definitely and control each soft The position of property container and orientation.Distinguish and follow the trail of position and the orientation of container with can determine, use In the operation that automatic anti-fault operation and key parameter are controlled.Mirror can be not sure to by any Other container is considered as the container needing to be eliminated.It also is able to eliminate any discriminating the most definitely and has been Become the container in crucial process segment.As long as can follow the tracks of the most continuously, container can retain Until the most appropriate superseded position on conveyer.Otherwise, each container should be at once Remove from conveyer.Product sequentially can be processed in sterile working the most transferredly.Fortune Send mechanism to rinse, and can be designed as using gaseous hydrogen peroxide technique decontamination. Whole features of conveyer can be applied cleaning aseptic design.Conveyer is each for other Individual crucial aseptic processing can be non-intrusion type.Under normal operating conditions, other are processed Any interference of function is all unacceptable.

Fig. 4 illustrates the aseptic formation of the flexible container according to an embodiment of the invention, fills out The process chart of the technique filled, seal and pack.The fabrication scheme of flexible container system can Aseptic formation, sterilizing, filling and sealing technology including integration.Fig. 4 illustrates for basis The preliminary process flow chart of the flexible container manufacture of the principle of the present invention and the embodiment party of device layout Formula.

In the diagram, technique is from the beginning of step 402.In this step, the technique forming container Can as required or expectation, in ISO 8 (100,000 grades) toilet, locally HEPA Filter and carry out under deionized stick.The volume of main film and aluminium barrier material is loaded into former. It follows that in step 404a and 404b, it is possible to use the contact main film of roller system clean Contact side and interior contact side relatively, and accumulated by a series of rollers.In step 406 In, it is possible to the peelable aluminum foil strip covering API chamber is cut to size, and with removable molten Close and be stacked on main film with strip.In this step, paper tinsel can manual load or automatically load.

It follows that in a step 408, folding film, and paper tinsel is die-cut to two, lay To two different height, respectively above and below film.Then paper tinsel is cut to length also It is transferred to container film, fuses in the top of the film folded and bottom.

The one-level that can generate separation diluent chamber and medicine chamber in step 410 is peelable close Envelope.One-level peelable seal can be formed as being perpendicular to the straight line of two sides of laminate film, or Can be for bending, zigzag or other shapes.It follows that in step 412, it is possible to Along film length by fold main diaphragm seal together, generate side periphery seal.? In another embodiment, main film can be arranged in above secondary film, and along each Two film fusions or other modes are sealed by the length of individual side.In another embodiment, One-level peelable seal was formed before peripheral sealing.

In step 414 and 416, it is possible to cutting separate single from main film roll subsequently Empty, and position in step 420, thus be automatically loaded sterile field.And, In one embodiment, in step 418, it is possible to from production line, machinery removes from cutting The fragment of step.

This time point in process, flexible container is formed to be had: the periphery that part seals Upper chamber, wherein the top of upper chamber is formed with opening；And it is relative with upper chamber Lower chamber, lower chamber has the periphery that part seals similarly, but in lower chamber Bottom is formed with opening.Upper chamber can be separated with lower chamber by one-level peelable seal, And the opening of upper chamber can be the most relative with the opening of lower chamber.Thus, at this Time point, from the front viewing of the flexible container that part builds, laminate part can form substantially H Shape.It follows that in step 422, it is possible to assess the airtight quality of container and will have The bag of defect removes from assembly line.

It follows that in step 424, flexible container is transferred to interface chamber, this chamber, interface Room forms offer interface between region and electron beam chamber at the container of production line.In this step, In one embodiment, now can actuating element build flexible container so that part structure The flexible container built positions with vertical orientation that (that is, upper chamber is opening up, with the most at present Portion's chamber opening down).This manipulation, described control can be realized by using various controllers Device processed such as CPU (CPU), server, personal computer (PC), can compile Journey logic control (PLC) mechanism, robot cell and other devices.Controller can be configured to Direction and/or power is provided to various mechanical devices, to the flexible container that part builds Expect to handle effectively.For instance, it is possible to arrange mechanical arm, including can pick-up build soft Property container the sucker being placed on mandrel.Mandrel can include carrying a certain amount of such as nitrogen The air-blast atomizer of the fluid of gas, it can make the opening of lower chamber expand, thus be easily positioned at core On axle.Mandrel can be built into the flexible container transporting part structure by after manufacturing process On the pallet of continuous step or retainer.Alternately, including electrostatic charge, clamp structure, magnet Other mechanical arm can be used in pickup and transport portion build flexible container to mandrel or its The structure of his holding means.Another replacement scheme is to use cam or friction feed bowl technology, The flexible container that part is built by gravity or vibration orients from the first displacement to second, So that the flexible container that part builds can be delivered to sterile field by retainer.

It addition, in step 424, after bag shapes, it is possible to the flexible container that part is built Importing sterile field, such as low pressure (300KeV) electron beam chamber, hydrogen peroxide are cleaned or it His sterilizing machining area.Sterile field can be positioned at the same of the flexible container of forming part structure In toilet.Thus, it is undesirable to by part build flexible container move to separate facility or Space, but can keep " online " on the contrary so that if necessary, from being formed Sterilizing returns the processing of filling and can carry out the most in order.This " online " work Skill allows to manufacture quickly flexible container, and allows the control sterilization process of higher degree (to subtract The chance of of low pollution, thus reduce defect).Similarly, " online " technique energy of the disclosure Enough significantly decrease and remove the flexible container of part structure also with from first or " shaping " toilet The flexible container that part builds is transported to second " sterilizing " or " electron beam " toilet, so After again carry or be transmitted back to first or other toilets with fill and ultimately form or hermetic unit The cost that the flexible container built is associated.

As mentioned above, it is possible to the flexible container that each part builds is automatically placed in and transports system continuously System, the flexible container that part builds is delivered to sterilization process by this continuous delivery system, such as electricity Son bundle sterilizing.Especially, it is possible to commanding apparatus, software and/or hardware are set, part is built Flexible container be orientated and be properly exposed to electron beam emitter.Alternately, it is possible to by soft Property container be placed in interval/indexing delivery system.

In the embodiment illustrated in fig. 4, in step 427, the first side of irradiation bag, then exists Step 428 overturns bag.It follows that the second side of irradiation bag in step 430.

The delivery system transporting bag can include 180 ° of rotating mechanisms, to guarantee that electron beam irradiation is only The flexible container that part builds is completely penetrated through by single path.In one embodiment, energy Enough it is incorporated to adequate shielding to conveyer or retainer, to guarantee the flexibility that stop portions builds A part for container is not by electron beam irradiation so that this part of the flexible container that part builds is not It is excessively exposed to electron beam.Such as, whole face exposure of the container formed such as fruit part are in electricity The irradiation of son bundle, container back side diluent and buffer chamber that part is formed are not affected by shining by shielding Penetrate so that API chamber becomes the container of part formation and is exposed to the electron beam irradiation of dorsal part only A part.Transportation system can transport single container continuously and pass through Low-voltage Electronic with constant speed Bundle chamber, to guarantee that they accept suitable electron-beam dose, meets required sterilizing and ensures water Flat.

In another embodiment, transportation system can include the single electricity with two windows Zi Shu mechanism, in order to the both sides of exposure cage.In this embodiment, the side of exposure cage, Then before being exposed to the second window, container is turned over turnback.In another embodiment, It is provided with multiple electron beam mechanism.Such as, the flexible container that part builds can be simultaneously or sequentially Pass through from the first and second electron beam mechanism fronts, to carry out required sterilization process.When simultaneously By time, electron beam device can each other faced by.Alternately, electron beam device can It is spaced, and is positioned at the both sides of transportation system's line.First and/or second electron beam mechanism can It is provided with shielding body, or avoids the flexible appearance that part is built in a similar way as described above The mode of device over-exposure orients or targeting.It is of course possible to increase extra along transportation system's line Electron beam equipment, and can as desired to point to.It addition, the screen of replacement can be arranged Cover arrangement, to prevent diluent and the over-exposure of buffer chamber of the container to part is formed.

After the flexible container sterilizing that part builds, it is transported to them use in step 432 In the main isolation part filled, such as ISO 5 (100 grades) isolation part.In selectable step In 434, it is possible to check that each bag is to judge whether it is appropriately irradiated.The bag of non-suitable radiation Can be rolled off the production line as superseded bag.Alternately, the whole manufacturing process energy of flexible container Enough complete in isolation part.Under any circumstance, each above-mentioned processing step can be same clean Carry out in clean room, to avoid and to transport what flexible container was associated during manufacture outside toilet Cost, time and possible production error.

About above referenced electron beam sterilization technique, carry out the assessment of voltage dosage map, Thus the information put about the high spot relevant to electron beam irradiation exposure and " cold " is provided. Based on intended biological load level, minimum electron-beam dose is set as 18kGy, is simultaneously based on The functional test of container integrity judges the maximum electron beam dosage allowed.It is exposed to more than 70 The electron beam irradiation of kGy can produce impact to the character of plastics, particularly polypropylene and PET.

After sterilizing, in step 436, then the flexible container that part builds can be inserted machine In dynamicization system, chain system or linear electric motors that such as interval is fixing position (puck) system, Its flexible container each part built individually is carried through filling and sealing technology.As above institute Stating, empty (part builds) flexible container can be orientated in linear electric motors alignment system API/ dose chamber opening up.Then in step 438, empty container can be transported to medicine Product dosing system, medicine dosing system is by medicament or API dosage to medicine/upper chamber.? In selectable step 440, it is possible to weighing container before fill container with medicament/API.? In step 442, select medicament/API.Medicament/API can be various forms, including powder shape Formula, gel, liquid form, capsule, sheet, a combination thereof etc..Such as, in step 450, By the aseptic transfer port system of standard, the sterile powder medicament/API of batch can be supplied extremely Spiral fill system.Alternately, in step 448, it is possible to by a series of sterilising filtrations Sterilized liquid medicament/API is supplied to mass flow pump by device group.Medicament/API chamber can be passed through In the relatively large direct delivery of medicaments/API of opening, its can reduce spill-out and allow more accurate True and faster fill rate.As shown in Figure 4, it is possible to before filling with medicament/API, right N implemented by bag₂Purging.The filling of powder or liquid A PI can also manually or mechanically be carried out.

In step 452, it is possible to generate after medicament/API fills and separate medicine chamber and biography Send or two grades of peelable seals of buffer chamber.In step 454, it is possible to fill at medicament/API Weighing container afterwards, confirms suitable filling weight.For the filling of liquid preparation/API, energy Mass flow pump is enough set, packing volume is provided continuous print feedback.

It follows that in step 458, container being transported to port and inserts board, it is by port It is automatically inserted into transmission or buffer chamber, and generates the sealing of Guan Bi for port.Can be by port Sterilizing in advance.Now, in step 460, the lower end of flexible container is by closing this part of container Peripheral sealing fully form.Selectively, additionally it is possible to check bag in this stage of technique, And defective bag can be removed from processing line.

It follows that in step 462, it is possible to container is rotated 180 ° (or other angles), The opening upwards of diluent chamber is oriented, and in step 464, container is transported to dilution Board is filled in agent.Rotation can complete in every way, including using feed or vibrating basin technology； Use the gravity flexible container that makes part build clear the jumps " falling " (be filled with API to fill out Fill chamber and heavier than diluent chamber) and be kept device dish or keep structure " card is caught "； Use and there is fixture, magnet, electrostatic, sucker or the mechanical arm of other holding commanding apparatus, make The mechanical arm structure flexible container that rotating part builds along width or the X direction of container.When So, class can be directly incorporated in the retainer transporting the flexible container that part builds or locator As technology.

In addition, retainer or location can directly be handled by above-mentioned various methods and technology Device (replaces directly processing the flexible container that part builds).Thus, retainer, locator (puck) Or conveyer belt self can " overturn ", to allow be filled with medicament/API and be mounted with port Filling to diluent chamber afterwards.Be also to be understood that and be fabricated and inserted into port and the closeest The technique of envelope can carry out simultaneously or carry out respectively.

Then, in step 466, use mass flow pump by diluent by sterilising filter group Dosage, and then in step 468, conveying containers is diluted agent and seals.In step 470 In, container is indexed into next board, generates final diluent and seal.Then in step 472 In, container is transported to removal board, here container is removed from motorised systems and in order to Step 474 suitably removes from isolation network and orients.

In step 476, container exits isolation part, carries out various " finishing operations ".Example As, in step 478, rinse drying receptacle.Then, in step 480, bag is carried out Final cutting, removes fragment from production line.Then a series of test is carried out, including step 482 In weight check, in step 484 Crack Detection test and step 486 in PM inspection Test.Eliminate any underproof container in these tests, and remove from production line.

It follows that can be that bag is labelled in step 488, fold also in step 490 Fix and be packaged in container in step 492.Finally, in step 494, it is possible to It is used for transporting by each packaging palletize accommodating multiple containers.

Compared with traditional manufacturing technology, by eliminating the waste material in both material member and processing, The manufacturing process cost of the flexible container of the disclosure is lower.In one embodiment, work is manufactured Skill only relates to three primary clusterings (main film, peelable paper tinsel and port).It addition, the disclosure Manufacturing process single integrated at Wiring technology by manufacture is merged into, eliminate processing and Waste in process, should include at Wiring technology: bag shapings, the filling of online electron beam sterilization, bag, And include the final sealing of port.By increasing the output capacity of the manufacturing process of the disclosure, Achieve the further minimizing of unit cost.

Although the most in detail and with reference to illustrative embodiments, invention has been described, but right For those skilled in the art, it is clear that can adopt in the case of without departing substantially from disclosure scope With various changes and equivalent.

Claims (16)

1. for manufacturing a system for flexible pouch, including:

Single enclosed environment, this single enclosed environment is configured to sterile processing；

Flexible pouch manufactures board, and this flexible pouch manufactures board and is configured to manufacture flexible pouch and be positioned at In described enclosed environment；

Electron beam sterilization board, this electron beam sterilization board is configured to described flexible pouch sterilizing also And be positioned in described single enclosed environment；And

Filling board, this filling board is configured to fill described flexibility with at least two different materials Bag, and this filling board is positioned at described single enclosed environment.

System the most according to claim 1, also includes:

Packing machine station, this packing machine station is configured to filling described soft with the two different materials Flexible pouch described in removal after property bag, and this packing machine station is positioned at described single enclosed environment.

System the most according to claim 1, also includes:

Transporting equipment, this transporting equipment is configured to move through described electron beam in described flexible pouch Described flexible pouch is kept during sterilizing board.

System the most according to claim 3, wherein,

Described electron beam sterilization board includes electron beam generator；And

Described transporting equipment is configured to rotate described flexible pouch so that at least the two of described flexible pouch Individual relative side is exposed to described electron beam generator.

System the most according to claim 1, wherein,

Described filling board is configured to fill the Part I of described flexible pouch with first fluid, and And it is described soft with at least one filling being different from the second fluid of described first fluid and powder The Part II of property bag.

System the most according to claim 1, wherein,

The two different materials includes at least one active constituents of medicine.

7. for the method manufacturing flexible pouch, including:

Generate flexible pouch；

After generating described flexible pouch, the most described flexible pouch is positioned over transport knot On structure；

Mobile described transport structure and described flexible pouch are through electron beam sterilization board, with to described Flexible pouch sterilizing；And

In mobile described transport structure and flexible pouch after described electron beam sterilization board, greatly Described flexible pouch is filled with two kinds of different materials at once on body.

Method the most according to claim 7, wherein

Described generation, place, mobile and fill and all carry out in identical single environment.

Method the most according to claim 7, also includes

Transport structure is set, and uses described transport structure to rotate described flexible pouch.

Method the most according to claim 9, also includes

Described transport structure is used to rotate described flexible pouch so that described flexible pouch more than one Side is by electron beam generator sterilizing.

11. methods according to claim 7, also include:

Arranging conveyer structure, described conveyer structure is used for moving described transport structure and flexibility Bag is through described electron beam sterilization board；And

At least one in described conveyer structure and described transport structure is used to rotate described flexibility Bag.

12. methods according to claim 7, also include:

Described flexible pouch is made board from flexible pouch and is directly transported to described electron beam sterilization machine Platform, and the most directly it is transported to fill board, wherein,

Described flexible pouch makes in board, described electron beam sterilization board and described filling board Each is positioned in identical single gnotobasis so that do not use the transfer knot environmentally separated Described flexible pouch is moved to described electron beam sterilization board and from described electron beam sterilization board by structure Mobile described flexible pouch.

13. methods according to claim 7, also include:

Only use automated machine structure that from flexible pouch, described flexible pouch is made board directly to transport To described electron beam sterilization board, and the most directly it is transported to fill board.

14. 1 kinds of systems being used for manufacturing the flexible container of filling, including:

Flexible container manufactures board, and this flexible container manufactures board and is configured to manufacture flexible container；

Electron beam sterilization board, this electron beam sterilization board is configured to described flexible container sterilizing；

Filling board, this filling board is configured to fill described flexibility with at least two different materials Container；

First conveyer belt, described flexible container manufacture board is connected directly to by this first conveyer belt Described electron beam sterilization board；And

Second conveyer belt, described electron beam sterilization board is connected directly to institute by this second conveyer belt State filling board.

15. systems according to claim 14, wherein,

Described flexible container manufacture board, described electron beam sterilization board, described filling board, Described first conveyer belt and described second conveyer belt are entirely located in identical single gnotobasis and surround In.

16. systems according to claim 14, also include:

Transporting equipment, this transporting equipment is configured to move through described electronics at described flexible container Keep described flexible container during bundle sterilizing board, and rotate described flexible container and make described soft At least two relative side of property container is exposed to the electronics being positioned in described electron beam sterilization board Beam generator.